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Investigating interleukin 17 secreting cell infiltration to understand racial disparities in colorectal cancer

Posted on:2015-09-24Degree:M.SType:Thesis
University:San Diego State UniversityCandidate:Shah, Jinel KFull Text:PDF
GTID:2474390017994739Subject:Biology
Abstract/Summary:
Colorectal cancer (CRC) is the third leading cause of cancer-associated deaths in developed countries. African Americans (AA) have a higher rate of sporadic CRC as compared to Caucasian Americans (CA) in the United States. Several studies have shown that cytotoxic immune cells infiltrating in the tumor microenvironment play a pivotal role in protection against the tumor but the question remains whether they play any role in racial disparity. Previous studies in our lab analyzed data from the North Carolina Colon Cancer Study (NCCCS), a population-based cohort (45% AA and 55% CA), for antitumor immune markers to understand their role in racial disparities in CRC. So far, our lab has analyzed CD8+, CD57+ and Granzyme B+ (GzmB) cell infiltration using immunohistochemistry. CD8+ cells are associated with better prognosis of CRC; however, there was no significant difference in their infiltration in the tumor tissues of the two races (p: 0.97). CD57, a marker for NK cells, also did not give significantly different results for AA and CA (p: 0.71). However, GzmB+ cell infiltration was significantly different, suggesting that AA are less protected from CRC as compared to CA (p: 0.014). To see if chronic inflammation is one of the underlying reasons for AA to have a lower cytotoxic response against CRC, my study compared the IL-17+ cell infiltration but saw no difference across the two races (p: 0.79). I next investigated the correlation of CD8+, CD57+ and IL-17+ cells with GzmB+ cell infiltration. The comparison of GzmB+ cell infiltration with the IL-17+ cell infiltration showed a direct association (p: 0.006) suggesting an antitumor role of IL-17+ cells. Also, GzmB correlated better with both CD8 and CD57+ cell infiltration in CA than in AA in samples that had less IL-17+ cells. Overall, my study showed that IL-17+ cells may not be a reason that AAs have lower cytotoxic immune responses against CRC.
Keywords/Search Tags:CRC, Cell infiltration, Il-17, Racial, CD8
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